4-Hydroxy-2-nonenal induces endothelial cell injury via PKCdelta and biphasic JNK activation
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Date
2008-03-10
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Abstract
4-Hydroxy-2-nonenal (4-HNE), a major product generated during oxidative stress, exhibits
cytotoxic effects; however, the mechanisms of 4-HNE-induced endothelial cell injury are not
well defined. To explore this issue, we examined how 4-HNE damages human umbilical vein
endothelial cells (HUVECs) and found that 4-HNE induced biphasic activation of c-Jun
N-terminal kinase (JNK). Both pre- and post-treatment of HUVECs with SP600125, a specific
JNK inhibitor, significantly suppressed the cytotoxic effects of 4-HNE. Inhibition of
protein kinase Cd (PKCd), which was also phosphorylated by 4-HNE, reduced endothelial
cell injury as well as late-phase JNK phosphorylation elicited by 4-HNE. Inversely,
pre-treatment of HUVECs with SP600125 suppressed PKCd activation. Taken together, these
results support the concept that 4-HNE induces vascular endothelial cell injury by the interaction
between biphasic JNK activation and the PKCd pathway.
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Keywords
4-Hydroxy-2-nonenal, Cd, cell injury, c-Jun N-terminal kinase, endothelial cell, kinase, oxidative stress, protein